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Amelioration of acute inflammation by systemic administration of a cell-permeable peptide inhibitor of NF-κB activation

✍ Scribed by Paola di Meglio; Angela Ianaro; Sankar Ghosh

Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
598 KB
Volume
52
Category
Article
ISSN
0004-3591

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✦ Synopsis

Abstract

Objective

We used an experimental model of inflammation in mice, carrageenan‐induced paw edema, to study the antiinflammatory effects of the NEMO‐binding domain (NBD) peptide, which blocks activation of the inducible transcription factor NF‐κB.

Methods

Paw edema was induced by subplantar injection of 1% λ‐carrageenan into the mouse left hind paw. Test agents were given intraperitoneally immediately after carrageenan injection. The increase in footpad thickness was considered to be edema. In some experiments, the mice were killed and the paws were removed for histologic and molecular biology analysis. NF‐κB DNA binding activity was evaluated in nuclear extracts by electrophoretic mobility shift assays. The expression levels of NF‐κB–regulated cyclooxygenase 2 (COX‐2) protein and tumor necrosis factor α (TNFα) messenger RNA (mRNA) were evaluated by immunoblot analysis and polymerase chain reaction amplification of reverse‐transcribed mRNA, respectively.

Results

We found that systemically administered NBD peptide significantly inhibited edema formation and cellular infiltration in inflamed mouse paws. This antiinflammatory activity was most likely due to inhibition of expression of proinflammatory mediators, such as TNFα and COX‐2, in inflamed tissues.

Conclusion

These studies further establish NF‐κB as a target for antiinflammatory therapy and provide support for the use of the NBD peptide as a possible therapeutic agent for inflammatory diseases.

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